A Study of Debio 025 in Combination With PegIFN Alpha-2a and Ribavirin in Chronic HCV Patients Non-responders to Standard Treatment

This is a multicentre, open-label, randomized, 5 arm parallel-group, multiple dose study in
50 chronic hepatitis C virus (HCV) genotype 1 non-responders to standard treatment with
peg-IFN alpha (2a or 2b) and ribavirin. The entire study lasts a maximum of 96 weeks and
consists of a 48- or 72-week treatment period (according to response). A follow-up visit to
assess the sustained viral response (SVR) takes place 24 weeks after treatment cessation,
i.e., at study Week 72 or 96, or earlier for discontinued study participants.

There were 2 parts in the treatment period. Part 1 lasted from Day 1 to Day 29 (Weeks 1 to
4); Part 2 lasted from Week 5 to Week 48 or 72.

During Part 1 of treatment (Weeks 1 to 4), participants are randomized to 1 of 5 treatment
arms and receive 4 weeks of Debio 025 (alisporivir) monotherapy, Debio 025 combined with
standard dose peg-IFNα2a, or 1 of 3 triple therapies combining different doses of Debio 025
with peg-IFNα2a and ribavirin at standard doses.

During Part 2 of treatment (Weeks 5 to 48 or 72), participants receive standard doses of
peg-IFNα2a/ribavirin dual therapy for 44 or 68 weeks, depending on their response to
treatment. At Week 12, participants who do not achieve ≥ 2 log10 decrease in HCV RNA are
withdrawn and considered treatment failures. Participants who have undetectable HCV RNA
levels and/or ≥ 2 log10 decrease in HCV RNA continue treatment until Week 24. At Week 24,
participants who still have detectable HCV RNA levels are withdrawn and considered treatment
failures. Participants with undetectable HCV RNA levels at Weeks 12 and 24 continue
treatment until Week 48. At Week 24, "slow responders" (defined as participants with a
detectable, but > 2 log10 decrease in HCV RNA levels at Week 12 and undetectable levels at
Week 24) are eligible to continue treatment until Week 72.

Inclusion Criteria:

- Male and female patients between 18 and 60 years of age.

- Hepatitis B negative and human immunodeficiency virus (HIV) negative.

- Diagnosed with hepatitis C genotype I and not responsive to treatments such as
peginterferon alpha-2a or 2b and ribavirin for at least 12 weeks.

- Adequate liver function (Child-Pugh-Turcotte score A) and other laboratory parameters
within acceptable range.

- Females may participate only if they cannot become pregnant, i.e., are surgically
sterile, post-menopausal, or using 2 reliable contraceptive methods.

- Male patients must be surgically sterile or utilizing a barrier contraceptive method.

- For female patients of child bearing potential, negative pregnancy test within 1 week
of first investigational product administration.

Exclusion Criteria:

- Treatment with any investigational drug within 6 months prior to the start of the
study.

- Ongoing or recent use of antiviral medication within 1 month before the start of the
study.

- A known bad reaction or intolerance to Debio 025, peginterferon alpha-2a, and/or
ribavirin.

- Presence or history of any severe related disease.